Aphthasol

CLINICAL PHARMACOLOGY

The mechanism of action by which amlexanox accelerates healing
of aphthous ulcers is unknown. In vitro studies have demonstrated amlexanox to
be a potent inhibitor of the formation and/or release of inflammatory mediators
(histamine and leukotrienes) from mast cells, neutrophils and mononuclear
cells. Given orally to animals, amlexanox has demonstrated anti-allergic and
anti-inflammatory activities and has been shown to suppress both immediate and
delayed type hypersensitivity reactions. The relevance of these activities of amlexanox
to its effects on aphthous ulcers has not been established.

Pharmacokinetics and Metabolism

After a single oral application of 100 mg of paste (5 mg amlexanox),
maximal serum levels of approximately 120 ng/ml are observed at 2.4 hours. Most
of the systemicabsorption of amlexanox is via the gastrointestinal tract, and
the amount absorbed directly through the active ulcer is not a significant
portion of the applied dose. The half-life for elimination was 3.5 +/- 1.1
hours in healthy individuals. Approximately 17% of the dose is eliminated into
the urine as unchanged amlexanox, a hydroxylated metabolite, and their conjugates.
With multiple applications four times daily, steady state levels were reached
within one week, and no accumulation was observed with up to four weeks of
usage.

Clinical Studies

The safety of amlexanox oral paste, 5%, was established in a
study in which 100 patients with aphthous ulcers applied the medication four
times daily for 28 days with no significant topical or systemic adverse
effects. The effectiveness was demonstrated in three controlled clinical
studies of patients with mild to moderate aphthous ulcers which evaluated 464 patients
receiving amlexanox oral paste, 5%, 465 patients receiving a placebo paste, and
195 patients receiving no treatment. Amlexanox oral paste, 5%, was shown to
accelerate healing of aphthous ulcers in a statistically significant manner as
compared to both vehicle and no treatment.

Amlexanox oral paste, 5%, versus no treatment

In the combined database of the two studies including a no
treatment group, there was a significant difference in the rate of ulcer
healing which translated to a reduction of 1.6 days in the median time to
complete healing and a reduction of 1.3 days in the median time to complete
pain relief. After 3 days of treatment there was a significant difference in
both percent of patients with complete healing of ulcers (21% vs. 8%) and
percent of patients with complete resolution of pain (44% vs. 20%).

Amlexanox oral paste, 5%, versus vehicle

In the combined database of the three studies, there was a
significant difference in the rate of ulcer healing which translated into a
reduction of 0.7 days in the median time to complete healing, and a reduction
of 0.7 days in the median time to complete pain relief. After 4 days of treatment
there was a significant difference in both percent of patients with complete
healing of ulcers (37% vs. 27%) and percent of patients with complete resolution
of pain (60% vs. 49%).

Pain relief occurred in conjunction with healing of the
ulcers. Amlexanox oral paste, 5%, by itself, was not shown to be an analgesic
medication. The safety and effectiveness of the product in immunocompromised
individuals has not been assessed.

Cumulative % of Patients with Healed Ulcers

Results for amlexanox, 5%, vs. vehicle are based on three clinical trials.
Results for amlexanox, 5%, vs. no treatment are based on two clinical trials.
* denotes statistically significant superiority of amlexanox, 5%, vs. vehicle
and no treatment.
# denotes statistically significant superiority of amlexanox, 5%, vs. no treatment.
Error bars represent Standard Error of the Mean.

Last reviewed on RxList: 6/2/2009
This monograph has been modified to include the generic and brand name in many instances.